Renin is a natural enzyme which is released into the blood from the kidney. It cleaves its natural substrate, angiotensinogen, releasing a decapeptide, angiotensin I. This is in turn cleaved by converting enzyme in the lung, kidney and other tissues to an octapeptide, angiotensin II. Angiotensin II raises blood pressure both directly by causing arteriolar constriction and indirectly by stimulating release of the sodium-retaining hormone aldosterone from the adrenal gland causing a rise in extracellular fluid volume. Inhibitors of renins have been sought as an agent for control of hypertension and hyperaldosteronism.
The present invention concerns novel peptides which inhibit renin. It also concerns pharmaceutical compositions containing these novel peptides, methods of treating renin-associated hypertension and hyperaldosteronism, as well as the use of the peptides as diagnostic tools, and the methods for preparing the peptides.
U.S. Pat. No. 4,479,941 covers certain renin-inhibitory peptides of the formula ##STR1##
European Application No. 85/308759 covers certain renin-inhibitory dipeptides of the formula ##STR2## wherein m is 0 or 1 and R.sup.1 -R.sup.5 are a variety of organic groups.
European Application No. 184,855 covers renin-inhibitory peptides of the formula ##STR3## wherein A is an N-protecting group; R.sub.1, R.sub.3, R.sub.5 and R.sub.7 are loweralkyl or lipophilic or aromatic amino acid side chains and may be the same or different; R.sub.2, R.sub.4 and R.sub.6 are hydrogen or loweralkyl and may be the same or different; X is hydrogen, loweralkyl or --CH.sub.2 OR.sub.8, wherein R.sub.8 is hydrogen, loweralkyl or alkaryl; and R.sub.9 is loweralkyl, hydroxy, hydroxyalkyl, alkoxy, allyl, alkaryloxy or thioalkyl and pharmaceutically acceptable salts thereof.